Christopher Bradfield
Professor of Oncology
Ph.D., Univ. of California at Berkeley, 1986
Postdoctoral Research: McArdle Laboratory, University of Wisconsin
Address: 213A McArdle
Telephone: 262-2024
E-mail: bradfield@oncology.wisc.edu
Research Interests:
Biological adaptation to environmental stress and carcinogen exposure
Research Fields:
Cancer Genetics
Gene Expression
Yeast and Fungi
Research Description: Our laboratory is interested in understanding how and why organisms respond to adverse physical and chemical environments. Our current area of research focus is on a family of transcriptional regulators known as PAS proteins. Members of this emerging family of proteins control a number of processes, including xenobiotic metabolism (Ah-receptor and Arnt), circadian rhythms (MOP3, MOP4, CLOCK, and PER), angiogenesis (HIF1a, HIF2a, HIF3a, ARNT, ARNT2 and MOP3),and neurogenesis (SIM1 and SIM2). The model system that is currently emphasized is the signal transduction pathway mediated by Ah-receptor/Arnt heterodimeric complex. These helix-loop-helix-PAS proteins regulate the induction of a number of xenobiotic metabolizing enzymes that occurs in response to exposure to a variety of polycyclic aromatic environmental pollutants. In addition, the Ah-receptor mediates a second battery of genes responsible for a number of “toxic effects” of dioxins, such as epithelial hyperplasia, immunosuppression, teratogenesis and tumor promotion.
To understand these proteins and their signal transduction pathways, we are focusing on the characterization of the Ah-receptor/Arnt pathway in genetically manipulable organisms such as mice and yeast. We use yeast genetics as a method to identify genes that are required for signaling. In addition, the yeast system is proving valuable in modifier screens to identify novel components of the dioxin signaling pathway. Experiments in the murine system help us to understand the physiological function of these proteins, as well as to identify new members of the PAS superfamily. Current areas of interest include the use of gene-targeting to generate informative bHLH-PAS loci and the use of more classical transgenic approaches to construct murine models that will help us characterize the mechanisms that underlie the toxicological and developmental effects of halogenated aromatics like dioxin.
Representative Publications:
Yao, G., Craven, M., Drinkwater, N. and Bradfield, C. A. 2004. Interaction Networks in Yeast Define and Enumerate the Signaling Steps of the Vertebrate Aryl Hydrocarbon Receptor PLOS Biol, 2:355-367.
LaPres, J.J., Glover, E., Dunham, E.E., Bunger, M.K., and Bradfield C.A. 2000. ARA9 Modifies Agonist Signaling through an Increase in Cytosolic Aryl Hydrocarbon Receptor. J. Biol. Chem. 275:6153-6159.
Hogenesch, J.B., Gu, Y.Z., Jain, S. and Bradfield, C.A. 1998. The basic-helix-loop- helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc. Natl Acad Sci USA 95:5274-547.
Maltepe, E., Schmidt, J.V., Baunoch, D., Bradfield, C.A., and Simon, M.C. 1997. Arnt is essential for responses to oxygen, glucose deprivation and developmental angiogenesis in the mouse. Nature. 386:403-40.
Schmidt, J.V., Su, GH, T., Reddy, J.K., Simon, M.C., and Bradfield, C.A. 1996. Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development Proc. Natl Acad Sci USA 93:6731-673.
Professor of Oncology
Ph.D., Univ. of California at Berkeley, 1986
Postdoctoral Research: McArdle Laboratory, University of Wisconsin
Address: 213A McArdle
Telephone: 262-2024
E-mail: bradfield@oncology.wisc.edu
Research Interests:
Biological adaptation to environmental stress and carcinogen exposure
Research Fields:
Cancer Genetics
Gene Expression
Yeast and Fungi
Our laboratory is interested in understanding how and why organisms respond to adverse physical and chemical environments. Our current area of research focus is on a family of transcriptional regulators known as PAS proteins. Members of this emerging family of proteins control a number of processes, including xenobiotic metabolism (Ah-receptor and Arnt), circadian rhythms (MOP3, MOP4, CLOCK, and PER), angiogenesis (HIF1a, HIF2a, HIF3a, ARNT, ARNT2 and MOP3),and neurogenesis (SIM1 and SIM2). The model system that is currently emphasized is the signal transduction pathway mediated by Ah-receptor/Arnt heterodimeric complex. These helix-loop-helix-PAS proteins regulate the induction of a number of xenobiotic metabolizing enzymes that occurs in response to exposure to a variety of polycyclic aromatic environmental pollutants. In addition, the Ah-receptor mediates a second battery of genes responsible for a number of “toxic effects” of dioxins, such as epithelial hyperplasia, immunosuppression, teratogenesis and tumor promotion.
Yao, G., Craven, M., Drinkwater, N. and Bradfield, C. A. 2004. Interaction Networks in Yeast Define and Enumerate the Signaling Steps of the Vertebrate Aryl Hydrocarbon Receptor PLOS Biol, 2:355-367.
